Metadichol® Inhibits Zoonotic Viruses Nipah, Lassa, and Rabies In Vitro: Evidence for the Vitamin D Receptor–MYC–SP1–GSPT1 Axis and Nuclear Receptor Modulation as Core Antiviral Mechanisms
Main Article Content
Abstract
Emerging and re-emerging zoonotic viruses, including Nipah virus, Lassa virus, and rabies virus, represent a persistent and escalating threat to global public health, for which no broadly effective antiviral agents currently exist. Metadichol®, a nanoemulsion of long-chain alcohols (policosanol), has previously demonstrated significant in vitro efficacy against diverse viruses including severe acute respiratory syndrome coronavirus 2 and Ebola virus. In this study, we present new in vitro data showing that Metadichol potently inhibits Lassa, Nipah, and rabies virus entry using a novel alphavirus-based pseudovirus platform, with half-maximal inhibitory concentration values of 831.7, 2455, and 2621 ng/mL, respectively, and no significant cytotoxicity in human embryonic kidney 293T cells.
We focus our mechanistic analysis on two core pathways that underpin this broad-spectrum activity. First, we describe the vitamin D receptor–MYC–specificity protein 1–G1 to S phase transition 1 axis, in which Metadichol activates the vitamin D receptor, leading to MYC-mediated repression of specificity protein 1 and consequent downregulation of G1 to S phase transition 1 (also known as eukaryotic release factor 3a), a translation termination factor recently validated as a druggable host dependency factor essential for the replication of Lassa, Ebola, and other viruses. Second, we examine Metadichol’s modulation of nuclear receptors—including neuron-derived orphan receptor 1, liver X receptor alpha, and peroxisome proliferator-activated receptor gamma—which suppress interferon regulatory factors and the interferon-beta promoter, thereby fine-tuning the innate immune response to prevent immunopathology while maintaining antiviral defense.
Together, these two mechanisms—direct replication blockade via G1 to S phase transition 1 inhibition and immune optimization via nuclear receptor modulation—provide a mechanistic framework for Metadichol’s observed broad-spectrum efficacy. Given that Metadichol is commercially available and non-toxic (median lethal dose > 5000 mg/kg in rats), these findings support its further clinical investigation as a host-directed antiviral agent.
Keywords:
Nipah virus, rabies virus, Lassa virus, Metadichol, GSPT1, vitamin D receptor, host-directed antiviral, nuclear receptors, peroxisome proliferator-activated receptor gamma, liver X receptor, broad-spectrum antiviral
Article Details
How to Cite
RAGHAVAN, Palayakotai R.
Metadichol® Inhibits Zoonotic Viruses Nipah, Lassa, and Rabies In Vitro: Evidence for the Vitamin D Receptor–MYC–SP1–GSPT1 Axis and Nuclear Receptor Modulation as Core Antiviral Mechanisms.
Medical Research Archives, [S.l.], v. 14, n. 3, mar. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7269>. Date accessed: 06 apr. 2026.
doi: https://doi.org/10.18103/mra.v14i3.7269.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Taylor LH, Latham SM, Woolhouse ME. Risk factors for human disease emergence. Philos Trans R Soc Lond B Biol Sci. 2001;356(1411):983-989. doi:10.1098/rstb.2001.0888
2. Jones KE, Patel NG, Levy MA, et al. Global trends in emerging infectious diseases. Nature. 2008;451(7181):990-993. doi:10.1038/nature06536
3. Morse SS, Mazet JA, Woolhouse M, et al. Prediction and prevention of the next pandemic zoonosis. Lancet. 2012;380(9857):1956-1965. doi:10.1016/S0140-6736(12)61684-5
4. Paules CI, Marston HD, Fauci AS. Coronavirus infections—more than just the common cold. JAMA. 2020;323(8):707-708. doi:10.1001/jama.2020.0757
5. Karesh WB, Dobson A, Lloyd-Smith JO, et al. Ecology of zoonoses: natural and unnatural histories. Lancet. 2012;380(9857):1936-1945. doi:10.1016/S0140-6736(12)61678-X
6. Chua KB, Bellini WJ, Rota PA, et al. Nipah virus: a recently emergent deadly paramyxovirus. Science. 2000;288(5470):1432-1435. doi:10.1126/science.288.5470.1432
7. Paton NI, Leo YS, Zaki SR, et al. Outbreak of Nipah-virus infection among abattoir workers in Singapore. Lancet. 1999;354(9186):1253-1256. doi:10.1016/S0140-6736(99)04379-2
8. Bossart KN, Zhu Z, Middleton D, et al. A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute Nipah virus infection. PLoS Pathog. 2009;5(10):e1000642. doi:10.1371/journal.ppat.1000642
9. Lo MK, Feldmann F, Gary JM, et al. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci Transl Med. 2019;11(494):eaau9242. doi:10.1126/scitranslmed.aau9242
10. World Health Organization. Nipah virus. Accessed January 2025. https://www.who.int/news-room/fact-sheets/detail/nipah-virus
11. Richmond JK, Baglole DJ. Lassa fever: epidemiology, clinical features, and social consequences. BMJ. 2003;327(7426):1271-1275. doi:10.1136/bmj.327.7426.1271
12. World Health Organization. Lassa fever. Accessed January 2025. https://www.who.int/news-room/fact-sheets/detail/lassa-fever
13. McCormick JB, King IJ, Webb PA, et al. Lassa fever: effective therapy with ribavirin. N Engl J Med. 1986;314(1):20-26. doi:10.1056/NEJM198601023140104
14. Salami K, Gsell PS, Gunnell A, et al. Meeting report: WHO consultation on accelerating Lassa fever vaccine development in endemic countries. Vaccine. 2020;38(15):3140-3147. doi:10.1016/j.vaccine.2020.01.017
15. World Health Organization. Rabies. Accessed January 2025. https://www.who.int/news-room/fact-sheets/detail/rabies
16. Jackson AC. Rabies: Scientific Basis of the Disease and Its Management. 3rd ed. Academic Press; 2013.
17. Keshwara R, Shiber S, Engber S, et al. A recombinant rabies virus expressing the Marburg virus glycoprotein is dependent upon antibody-mediated cellular cytotoxicity for protection against Marburg virus disease in a murine model. J Virol. 2019;93(6):e01865-18. doi:10.1128/JVI.01865-18
18. Flint SJ, Enquist LW, Racaniello VR, Skalka AM. Principles of Virology: Molecular Biology, Pathogenesis, and Control. 2nd ed. ASM Press; 2004.
19. Bekerman E, Einav S. Combating emerging viral threats. Science. 2015;348(6232):282-283. doi:10.1126/science.aaa3778
20. Kaufmann SHE, Dorhoi A, Hotchkiss RS, Bartenschlager R. Host-directed therapies for bacterial and viral infections. Nat Rev Drug Discov. 2018;17(1):35-56. doi:10.1038/nrd.2017.162
21. Zumla A, Rao M, Wallis RS, et al. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. Lancet Infect Dis. 2016;16(4):e47-e63. doi:10.1016/S1473-3099(16)00078-5
22. Kumar N, Sharma S, Kumar R, et al. Host-directed antiviral therapy. Clin Microbiol Rev. 2020;33(3):e00168-19. doi:10.1128/CMR.00168-19
23. Raghavan PR. Policosanol nanoparticles. US patent 8,722,093 B2. May 13, 2014; US patent 9,006,292 B2. April 14, 2015.
24. Raghavan PR. Metadichol® a nano lipid emulsion that expresses all 49 nuclear receptors in stem and somatic cells. Arch Clin Biomed Res. 2023;7:524-536. doi:10.26502/acbr.50170368
25. Raghavan PR. Metadichol®: a novel nanolipid formulation that inhibits SARS-CoV-2 and a multitude of pathological viruses in vitro. BioMed Res Int. 2022;2022:1558860. doi:10.1155/2022/1558860
26. Raghavan PR. In vitro inhibition of Zika virus by Metadichol®, a novel nano emulsion lipid. J Immunol Tech Infect Dis. 2016;5(4):2-6. doi:10.4172/2329-9541.1000151
27. Raghavan PR. Metadichol® induced high levels of vitamin C: case studies. Vitam Miner. 2017;6:169. doi:10.4172/2376-1318.1000169
28. Raghavan PR. Metadichol®-induced expression of sirtuins 1-7 in somatic and cancer cells. Med Res Arch. 2024;12(6). doi:10.18103/mra.v12i6.5371
29. Raghavan PR. Metadichol, a modulator that controls expression of Toll-like receptors in cancer cell lines. Br J Cancer Res. 2024;7(3):720-732. doi:10.31488/bjcr.198
30. Raghavan PR. Metadichol-induced expression of Toll receptor family members in peripheral blood mononuclear cells. Med Res Arch. 2024;12(8). doi:10.18103/mra.v12i8.5610
31. Raghavan PR. Metadichol: an agonist that expresses the anti-aging gene Klotho in various cell lines. Fortune J Health Sci. 2023;6:357-362. doi:10.26502/jbsb.5107066
32. Raghavan PR. Metadichol®-induced expression of circadian clock transcription factors in human fibroblasts. Med Res Arch. 2024;12(6). doi:10.18103/mra.v12i6.5371
33. Raghavan PR. Synergistic targeting of Krüppel-like factor and related signaling pathways by Metadichol: a multidimensional anticancer strategy. Med Res Arch. 2025;13(6). Accessed January 2025. https://esmed.org/MRA/mra/article/view/6583
34. Raghavan PR. Beyond rapamycin: Metadichol represents a new class of multi-target mTOR modulators. Med Res Arch. 2025;13(9). Accessed January 2025. https://esmed.org/MRA/mra/article/view/6876
35. Virongy Bioscience. Manassas, VA, USA. Accessed January 2024. https://virongy.com/
36. Virongy Bioscience. Technologies. Accessed January 2024. https://virongy.com/technologies/
37. Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T. The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3’-poly(A) tail of mRNA. J Biol Chem. 1999;274(24):16677-16680. doi:10.1074/jbc.274.24.16677
38. Zhouravleva G, Frolova L, Le Goff X, et al. Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. EMBO J. 1995;14(16):4065-4072. doi:10.1002/j.1460-2075.1995.tb00078.x
39. Raghavan PR. VDR inverse agonism by Metadichol enhances VDBP-mediated immunity. Preprints. 2025. doi:10.20944/preprints202506.0491.v1
40. Salehi-Tabar R, Nguyen-Yamamoto L, Tavassoli-Bhattacharya A, et al. Vitamin D receptor as a master regulator of the c-MYC/MXD1 network. Proc Natl Acad Sci U S A. 2012;109(46):18827-18832. doi:10.1073/pnas.1210037109
41. Gartel AL, Ye X, Goufman E, et al. Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Proc Natl Acad Sci U S A. 2001;98(8):4510-4515. doi:10.1073/pnas.081074898
42. Beishline K, Azizkhan-Clifford J. Sp1 and the ‘hallmarks of cancer.’ FEBS J. 2015;282(2):224-258. doi:10.1111/febs.13148
43. O’Connor L, Gilmour J, Bonifer C. The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease. Yale J Biol Med. 2016;89(4):513-525.
44. Fang J, Pietzsch C, Witwit H, et al. Proximity interactome analysis of Lassa polymerase reveals eRF3a/GSPT1 as a druggable target for host-directed antivirals. Proc Natl Acad Sci U S A. 2022;119(30):e2201208119. doi:10.1073/pnas.2201208119
45. Fang J, Welch JS, Bhagwat N, et al. Functional interactomes of the Ebola virus polymerase identified by proximity proteomics in the context of viral replication. Cell Rep. 2022;38(12):110544. doi:10.1016/j.celrep.2022.110544
46. Zhao S, Ho A, Meng S, et al. Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics. Cell Host Microbe. 2023;31(7):1197-1209.e6. doi:10.1016/j.chom.2023.05.030
47. He L, Yang Y, Guo J, et al. CC-90009, a cereblon E3 ligase modulator, exhibits antiviral efficacy against JEV in vitro and in vivo via targeted degradation of GSPT1 and viral NS5 protein. Pharmaceutics. 2025;17(12):1524. doi:10.3390/pharmaceutics17121524
48. Evans RM, Mangelsdorf DJ. Nuclear receptors, RXR, and the Big Bang. Cell. 2014;157(1):255-266. doi:10.1016/j.cell.2014.03.012
49. Tsutsumi T, Suzuki T, Shimoike T, et al. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002;35(4):937-946. doi:10.1053/jhep.2002.32470
50. Choi JY, Seo JY, Yoon YS, Lee YJ, Kim HS, Kang JL. Virus-induced differential expression of nuclear receptors and coregulators in dendritic cells: implication to interferon production. Mol Immunol. 2011;48(9-10):1072-1080. doi:10.1016/j.molimm.2011.02.010
51. Basler CF. Molecular pathogenesis of viral hemorrhagic fever. Semin Immunopathol. 2017;39(5):551-561. doi:10.1007/s00281-017-0637-x
52. Geisbert TW, Feldmann H, Broder CC. Animal challenge models of henipavirus infection and pathogenesis. Curr Top Microbiol Immunol. 2012;359:153-177. doi:10.1007/82_2012_208
53. Cui HL, Grant A, Mukhamedova N, et al. Stimulation of liver X receptor has potent anti-HIV effects in a humanized mouse model of HIV infection. J Pharmacol Exp Ther. 2015;354(3):376-383. doi:10.1124/jpet.115.224485
54. Morrow MP, Grant A, Mujawar Z, et al. Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1. Mol Pharmacol. 2010;78(2):215-225. doi:10.1124/mol.110.065029
55. Pereira-Montecinos C, Tischler ND, Bhattacharya N, et al. The liver X receptor agonist LXR 623 restricts flavivirus replication. Emerg Microbes Infect. 2021;10(1):1378-1389. doi:10.1080/22221751.2021.1947749
56. Sierra B, Triska P, Soares P, et al. OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans. PLoS Pathog. 2017;13(2):e1006220. doi:10.1371/journal.ppat.1006220
57. Pascual G, Fong AL, Ogawa S, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ. Nature. 2005;437(7059):759-763. doi:10.1038/nature03988
58. Lefterova MI, Haakonsson AK, Lazar MA, Mandrup S. PPARγ and the global map of adipogenesis and beyond. Trends Endocrinol Metab. 2014;25(6):293-302. doi:10.1016/j.tem.2014.04.001
59. Lupberger J, Croonenborghs T, Roca Suarez AA, et al. Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection. Nat Chem Biol. 2017;13(1):93-100. doi:10.1038/nchembio.2193
60. Alemán CL, Más R, Hernández C, et al. A 12-month study of policosanol oral toxicity in Sprague Dawley rats. Toxicol Lett. 1994;70(1):77-87. doi:10.1016/0378-4274(94)90147-3
61. Alemán CL, Más Ferreiro R, Puig MN, et al. Carcinogenicity of policosanol in Sprague-Dawley rats: a 24-month study. Teratog Carcinog Mutagen. 1994;14(5):239-249. doi:10.1002/tcm.1770140505
62. Alemán CL, Puig MN, Elías EC, et al. Carcinogenicity of policosanol in mice: an 18-month study. Food Chem Toxicol. 1995;33(7):573-578. doi:10.1016/0278-6915(95)00026-x
2. Jones KE, Patel NG, Levy MA, et al. Global trends in emerging infectious diseases. Nature. 2008;451(7181):990-993. doi:10.1038/nature06536
3. Morse SS, Mazet JA, Woolhouse M, et al. Prediction and prevention of the next pandemic zoonosis. Lancet. 2012;380(9857):1956-1965. doi:10.1016/S0140-6736(12)61684-5
4. Paules CI, Marston HD, Fauci AS. Coronavirus infections—more than just the common cold. JAMA. 2020;323(8):707-708. doi:10.1001/jama.2020.0757
5. Karesh WB, Dobson A, Lloyd-Smith JO, et al. Ecology of zoonoses: natural and unnatural histories. Lancet. 2012;380(9857):1936-1945. doi:10.1016/S0140-6736(12)61678-X
6. Chua KB, Bellini WJ, Rota PA, et al. Nipah virus: a recently emergent deadly paramyxovirus. Science. 2000;288(5470):1432-1435. doi:10.1126/science.288.5470.1432
7. Paton NI, Leo YS, Zaki SR, et al. Outbreak of Nipah-virus infection among abattoir workers in Singapore. Lancet. 1999;354(9186):1253-1256. doi:10.1016/S0140-6736(99)04379-2
8. Bossart KN, Zhu Z, Middleton D, et al. A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute Nipah virus infection. PLoS Pathog. 2009;5(10):e1000642. doi:10.1371/journal.ppat.1000642
9. Lo MK, Feldmann F, Gary JM, et al. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci Transl Med. 2019;11(494):eaau9242. doi:10.1126/scitranslmed.aau9242
10. World Health Organization. Nipah virus. Accessed January 2025. https://www.who.int/news-room/fact-sheets/detail/nipah-virus
11. Richmond JK, Baglole DJ. Lassa fever: epidemiology, clinical features, and social consequences. BMJ. 2003;327(7426):1271-1275. doi:10.1136/bmj.327.7426.1271
12. World Health Organization. Lassa fever. Accessed January 2025. https://www.who.int/news-room/fact-sheets/detail/lassa-fever
13. McCormick JB, King IJ, Webb PA, et al. Lassa fever: effective therapy with ribavirin. N Engl J Med. 1986;314(1):20-26. doi:10.1056/NEJM198601023140104
14. Salami K, Gsell PS, Gunnell A, et al. Meeting report: WHO consultation on accelerating Lassa fever vaccine development in endemic countries. Vaccine. 2020;38(15):3140-3147. doi:10.1016/j.vaccine.2020.01.017
15. World Health Organization. Rabies. Accessed January 2025. https://www.who.int/news-room/fact-sheets/detail/rabies
16. Jackson AC. Rabies: Scientific Basis of the Disease and Its Management. 3rd ed. Academic Press; 2013.
17. Keshwara R, Shiber S, Engber S, et al. A recombinant rabies virus expressing the Marburg virus glycoprotein is dependent upon antibody-mediated cellular cytotoxicity for protection against Marburg virus disease in a murine model. J Virol. 2019;93(6):e01865-18. doi:10.1128/JVI.01865-18
18. Flint SJ, Enquist LW, Racaniello VR, Skalka AM. Principles of Virology: Molecular Biology, Pathogenesis, and Control. 2nd ed. ASM Press; 2004.
19. Bekerman E, Einav S. Combating emerging viral threats. Science. 2015;348(6232):282-283. doi:10.1126/science.aaa3778
20. Kaufmann SHE, Dorhoi A, Hotchkiss RS, Bartenschlager R. Host-directed therapies for bacterial and viral infections. Nat Rev Drug Discov. 2018;17(1):35-56. doi:10.1038/nrd.2017.162
21. Zumla A, Rao M, Wallis RS, et al. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. Lancet Infect Dis. 2016;16(4):e47-e63. doi:10.1016/S1473-3099(16)00078-5
22. Kumar N, Sharma S, Kumar R, et al. Host-directed antiviral therapy. Clin Microbiol Rev. 2020;33(3):e00168-19. doi:10.1128/CMR.00168-19
23. Raghavan PR. Policosanol nanoparticles. US patent 8,722,093 B2. May 13, 2014; US patent 9,006,292 B2. April 14, 2015.
24. Raghavan PR. Metadichol® a nano lipid emulsion that expresses all 49 nuclear receptors in stem and somatic cells. Arch Clin Biomed Res. 2023;7:524-536. doi:10.26502/acbr.50170368
25. Raghavan PR. Metadichol®: a novel nanolipid formulation that inhibits SARS-CoV-2 and a multitude of pathological viruses in vitro. BioMed Res Int. 2022;2022:1558860. doi:10.1155/2022/1558860
26. Raghavan PR. In vitro inhibition of Zika virus by Metadichol®, a novel nano emulsion lipid. J Immunol Tech Infect Dis. 2016;5(4):2-6. doi:10.4172/2329-9541.1000151
27. Raghavan PR. Metadichol® induced high levels of vitamin C: case studies. Vitam Miner. 2017;6:169. doi:10.4172/2376-1318.1000169
28. Raghavan PR. Metadichol®-induced expression of sirtuins 1-7 in somatic and cancer cells. Med Res Arch. 2024;12(6). doi:10.18103/mra.v12i6.5371
29. Raghavan PR. Metadichol, a modulator that controls expression of Toll-like receptors in cancer cell lines. Br J Cancer Res. 2024;7(3):720-732. doi:10.31488/bjcr.198
30. Raghavan PR. Metadichol-induced expression of Toll receptor family members in peripheral blood mononuclear cells. Med Res Arch. 2024;12(8). doi:10.18103/mra.v12i8.5610
31. Raghavan PR. Metadichol: an agonist that expresses the anti-aging gene Klotho in various cell lines. Fortune J Health Sci. 2023;6:357-362. doi:10.26502/jbsb.5107066
32. Raghavan PR. Metadichol®-induced expression of circadian clock transcription factors in human fibroblasts. Med Res Arch. 2024;12(6). doi:10.18103/mra.v12i6.5371
33. Raghavan PR. Synergistic targeting of Krüppel-like factor and related signaling pathways by Metadichol: a multidimensional anticancer strategy. Med Res Arch. 2025;13(6). Accessed January 2025. https://esmed.org/MRA/mra/article/view/6583
34. Raghavan PR. Beyond rapamycin: Metadichol represents a new class of multi-target mTOR modulators. Med Res Arch. 2025;13(9). Accessed January 2025. https://esmed.org/MRA/mra/article/view/6876
35. Virongy Bioscience. Manassas, VA, USA. Accessed January 2024. https://virongy.com/
36. Virongy Bioscience. Technologies. Accessed January 2024. https://virongy.com/technologies/
37. Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T. The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3’-poly(A) tail of mRNA. J Biol Chem. 1999;274(24):16677-16680. doi:10.1074/jbc.274.24.16677
38. Zhouravleva G, Frolova L, Le Goff X, et al. Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. EMBO J. 1995;14(16):4065-4072. doi:10.1002/j.1460-2075.1995.tb00078.x
39. Raghavan PR. VDR inverse agonism by Metadichol enhances VDBP-mediated immunity. Preprints. 2025. doi:10.20944/preprints202506.0491.v1
40. Salehi-Tabar R, Nguyen-Yamamoto L, Tavassoli-Bhattacharya A, et al. Vitamin D receptor as a master regulator of the c-MYC/MXD1 network. Proc Natl Acad Sci U S A. 2012;109(46):18827-18832. doi:10.1073/pnas.1210037109
41. Gartel AL, Ye X, Goufman E, et al. Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Proc Natl Acad Sci U S A. 2001;98(8):4510-4515. doi:10.1073/pnas.081074898
42. Beishline K, Azizkhan-Clifford J. Sp1 and the ‘hallmarks of cancer.’ FEBS J. 2015;282(2):224-258. doi:10.1111/febs.13148
43. O’Connor L, Gilmour J, Bonifer C. The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease. Yale J Biol Med. 2016;89(4):513-525.
44. Fang J, Pietzsch C, Witwit H, et al. Proximity interactome analysis of Lassa polymerase reveals eRF3a/GSPT1 as a druggable target for host-directed antivirals. Proc Natl Acad Sci U S A. 2022;119(30):e2201208119. doi:10.1073/pnas.2201208119
45. Fang J, Welch JS, Bhagwat N, et al. Functional interactomes of the Ebola virus polymerase identified by proximity proteomics in the context of viral replication. Cell Rep. 2022;38(12):110544. doi:10.1016/j.celrep.2022.110544
46. Zhao S, Ho A, Meng S, et al. Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics. Cell Host Microbe. 2023;31(7):1197-1209.e6. doi:10.1016/j.chom.2023.05.030
47. He L, Yang Y, Guo J, et al. CC-90009, a cereblon E3 ligase modulator, exhibits antiviral efficacy against JEV in vitro and in vivo via targeted degradation of GSPT1 and viral NS5 protein. Pharmaceutics. 2025;17(12):1524. doi:10.3390/pharmaceutics17121524
48. Evans RM, Mangelsdorf DJ. Nuclear receptors, RXR, and the Big Bang. Cell. 2014;157(1):255-266. doi:10.1016/j.cell.2014.03.012
49. Tsutsumi T, Suzuki T, Shimoike T, et al. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002;35(4):937-946. doi:10.1053/jhep.2002.32470
50. Choi JY, Seo JY, Yoon YS, Lee YJ, Kim HS, Kang JL. Virus-induced differential expression of nuclear receptors and coregulators in dendritic cells: implication to interferon production. Mol Immunol. 2011;48(9-10):1072-1080. doi:10.1016/j.molimm.2011.02.010
51. Basler CF. Molecular pathogenesis of viral hemorrhagic fever. Semin Immunopathol. 2017;39(5):551-561. doi:10.1007/s00281-017-0637-x
52. Geisbert TW, Feldmann H, Broder CC. Animal challenge models of henipavirus infection and pathogenesis. Curr Top Microbiol Immunol. 2012;359:153-177. doi:10.1007/82_2012_208
53. Cui HL, Grant A, Mukhamedova N, et al. Stimulation of liver X receptor has potent anti-HIV effects in a humanized mouse model of HIV infection. J Pharmacol Exp Ther. 2015;354(3):376-383. doi:10.1124/jpet.115.224485
54. Morrow MP, Grant A, Mujawar Z, et al. Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1. Mol Pharmacol. 2010;78(2):215-225. doi:10.1124/mol.110.065029
55. Pereira-Montecinos C, Tischler ND, Bhattacharya N, et al. The liver X receptor agonist LXR 623 restricts flavivirus replication. Emerg Microbes Infect. 2021;10(1):1378-1389. doi:10.1080/22221751.2021.1947749
56. Sierra B, Triska P, Soares P, et al. OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans. PLoS Pathog. 2017;13(2):e1006220. doi:10.1371/journal.ppat.1006220
57. Pascual G, Fong AL, Ogawa S, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ. Nature. 2005;437(7059):759-763. doi:10.1038/nature03988
58. Lefterova MI, Haakonsson AK, Lazar MA, Mandrup S. PPARγ and the global map of adipogenesis and beyond. Trends Endocrinol Metab. 2014;25(6):293-302. doi:10.1016/j.tem.2014.04.001
59. Lupberger J, Croonenborghs T, Roca Suarez AA, et al. Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection. Nat Chem Biol. 2017;13(1):93-100. doi:10.1038/nchembio.2193
60. Alemán CL, Más R, Hernández C, et al. A 12-month study of policosanol oral toxicity in Sprague Dawley rats. Toxicol Lett. 1994;70(1):77-87. doi:10.1016/0378-4274(94)90147-3
61. Alemán CL, Más Ferreiro R, Puig MN, et al. Carcinogenicity of policosanol in Sprague-Dawley rats: a 24-month study. Teratog Carcinog Mutagen. 1994;14(5):239-249. doi:10.1002/tcm.1770140505
62. Alemán CL, Puig MN, Elías EC, et al. Carcinogenicity of policosanol in mice: an 18-month study. Food Chem Toxicol. 1995;33(7):573-578. doi:10.1016/0278-6915(95)00026-x